Mechanisms of type-I- and type-II-interferon-mediated signalling

Abstract

Interferons are cytokines that have antiviral, antiproliferative and immunomodulatory effects. Because of these important properties, in the past two decades, major research efforts have been undertaken to understand the signalling mechanisms through which these cytokines induce their effects. Since the original discovery of the classical JAK (Janus activated kinase)-STAT (signal transducer and activator of transcription) pathway of signalling, it has become clear that the coordination and cooperation of multiple distinct signalling cascades - including the mitogen-activated protein kinase p38 cascade and the phosphatidylinositol 3-kinase cascade - are required for the generation of responses to interferons. It is anticipated that an increased understanding of the contributions of these recently identified pathways will advance our current thinking about how interferons work.

Function of HNRNPC in breast cancer cells by controlling the dsRNA‐induced interferon response

“…In addition, the type I interferon production can also be activated by the PRRs sensing the endogenous nucleic acids under stress conditions such as radiation, autoimmune disease, and cancer (West et al , 2015; Roers et al , 2016). Specifically, upon activation by their ligands, the cytoplasmic DNA sensors (ALR and cGAS) and RNA sensors (RIG‐I and MDA5) initiate the signaling cascade of interferon response (Honda et al , 2006; Goubau et al , 2013; Wu & Chen, 2014; McNab et al , 2015), leading to transcription of the ISGs (Platanias, 2005; Schneider et al , 2014). These interferon responses have been shown to be involved in regulating tumor development due to its well‐characterized pro‐apoptotic and anti‐proliferative effects in various types of cancer cells, including myeloma cell lines (Chen et al , 2001), lymphoma (Yang et al , 2013), liver cancer cells (Maeda et al , 2014; Murata et al , 2006; Sangfelt et al , 1997), and sarcoma cell lines (Sanceau et al , 2000).…”

Mnk kinases in cytokine signaling and regulation of cytokine responses

“…Interferons (IFNs) exhibit antineoplastic and antiviral properties and modulate immune responses [78,79]. Type I IFNs include IFNα, IFNβ, IFNω, IFNδ, IFNε IFNκ, IFNτ and other IFNs characterized by their selective binding to a common cell surface receptor, the Type I IFN receptor (IFNR) [78,79].…”

“…Type I IFNs include IFNα, IFNβ, IFNω, IFNδ, IFNε IFNκ, IFNτ and other IFNs characterized by their selective binding to a common cell surface receptor, the Type I IFN receptor (IFNR) [78,79]. Receptor-associated JAK kinases are then activated and control phosphorylation of signal transducers and activators of transcription (STAT) proteins [78,79].…”

“…Type I IFNs include IFNα, IFNβ, IFNω, IFNδ, IFNε IFNκ, IFNτ and other IFNs characterized by their selective binding to a common cell surface receptor, the Type I IFN receptor (IFNR) [78,79]. Receptor-associated JAK kinases are then activated and control phosphorylation of signal transducers and activators of transcription (STAT) proteins [78,79]. This results in formation and nuclear translocation of different DNA binding complexes important for transcription including the ISGF3 (IFN stimulated gene factor 3) complex consisting of phosphorylated STAT1, STAT2 and IRF-9, which regulates transcription via binding to ISREs (IFN stimulated response elements) [78,79].…”

“…Receptor-associated JAK kinases are then activated and control phosphorylation of signal transducers and activators of transcription (STAT) proteins [78,79]. This results in formation and nuclear translocation of different DNA binding complexes important for transcription including the ISGF3 (IFN stimulated gene factor 3) complex consisting of phosphorylated STAT1, STAT2 and IRF-9, which regulates transcription via binding to ISREs (IFN stimulated response elements) [78,79]. IFNγ is the only known type II IFN, and it mediates its effects by binding to a cell surface receptor consisting of IFNGR1 and IFNGR2 chains which are associated with JAK1 and JAK2, respectively [78,79].…”